Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai 400 019, India.
AAPS PharmSciTech. 2009;10(3):935-42. doi: 10.1208/s12249-009-9284-4. Epub 2009 Jul 24.
The present study demonstrates feasibility of preparation of nanoparticles using a novel polymer, polyethylene sebacate (PES), and its application in the design of drug-loaded nanocarriers. Silymarin was selected as a model hydrophobic drug for the present study. Two methods of preparation, viz., nanoprecipitation and emulsion solvent diffusion, were evaluated for preparation of nanoparticles. Effect of surfactants polyvinyl alcohol (PVA), lutrol F 68, and Tween 80 on the preparation of blank and silymarin-loaded PES nanoparticles was evaluated. Nanoprecipitation resulted in the formation of nanoparticles with all the surfactants (<450 nm). Increase in surfactant concentration resulted in decrease in entrapment efficiency and particle size except with PVA. The type and concentration of surfactant was critical to achieve low size and adequate drug entrapment. While increase in concentration of PES resulted in larger nanoparticles, inclusion of acetone in the organic phase resulted in particles of smaller size. In case of emulsion solvent diffusion, nanoparticles were obtained only with lutrol F 68 as surfactant and high surfactant concentration. The study revealed nanoprecipitation as a more versatile method for preparation of PES nanoparticles. Scanning electron microscopy studies revealed spherical shape of nanoparticles. Freeze-dried nanoparticles exhibited ease of redispersion, with a marginal increase in size. Differential scanning calorimetry and X-ray diffraction analysis revealed amorphous nature of the drug. The study demonstrates successful design of PES nanoparticles as drug carriers.
本研究证明了使用新型聚合物——癸二酸聚乙烯(PES)制备纳米颗粒的可行性,以及将其应用于设计载药纳米载体。水飞蓟素被选为本研究的模型疏水性药物。采用了两种制备方法,即纳米沉淀法和乳液溶剂扩散法,来制备纳米颗粒。考察了聚乙烯醇(PVA)、泊洛沙姆 F68 和吐温 80 等表面活性剂对空白和载水飞蓟素 PES 纳米颗粒的制备效果。所有表面活性剂(<450nm)都可以通过纳米沉淀法形成纳米颗粒。除了 PVA 之外,表面活性剂浓度的增加会导致包封效率和粒径的降低。表面活性剂的类型和浓度对获得低粒径和足够的药物包封至关重要。虽然 PES 浓度的增加会导致较大的纳米颗粒,但在有机相中加入丙酮会导致颗粒更小。对于乳液溶剂扩散法,只有使用泊洛沙姆 F68 作为表面活性剂且表面活性剂浓度较高时,才能得到纳米颗粒。研究表明,纳米沉淀法是制备 PES 纳米颗粒的一种更通用的方法。扫描电子显微镜研究显示纳米颗粒呈球形。冷冻干燥的纳米颗粒易于再分散,粒径略有增加。差示扫描量热法和 X 射线衍射分析表明药物呈无定形状态。该研究成功设计了 PES 纳米颗粒作为药物载体。